Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase

Arsun Bektas, Yongqing Zhang, Elin Lehmann, William H. Wood, Kevin G. Becker, Karen Madara, Luigi Ferrucci, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

Abstract

Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dys-regulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation gene expression mediated by the transcription factor NF-κB is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-κB -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-κB up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3- kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dys-regulated basal NF-κB activity may contribute to the mild pro-inflammatory state of aging.

Original languageEnglish (US)
Pages (from-to)957-974
Number of pages18
JournalAging
Volume6
Issue number11
StatePublished - 2014
Externally publishedYes

Keywords

  • CD4+ T cells
  • Gene expression
  • Human aging
  • NF-κB
  • PI3K

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint Dive into the research topics of 'Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase'. Together they form a unique fingerprint.

Cite this